Arras, Bioethics Panel Face Toughest Test Yet With Anthrax Vaccine Research on Children

Serving on the Presidential Commission for the Study of Bioethical Issuessince 2010, University of Virginia bioethicist John Arras has helped the commission tackle four major ethical questions. The latest one, the subject of a report issued Tuesday, was “by far” the most difficult, he said.

The national commission grappled with protecting children from anthrax and other agents that might be used in a bioterror attack. With no risk-free option, the commission faced “a true moral dilemma,” Arras explained.

In 2011, the U.S. government conducted a bioterrorism preparedness exercise to study the likely results of a large-scale release of weaponized anthrax spores in a city such as San Francisco. The casualty estimates were staggering: almost 8 million people would be affected, nearly a quarter of them children.

If such an event were to occur, current federal plans call for immediate distribution of antibiotics proven effective in treating anthrax infections, and follow-up widespread vaccination against anthrax, because anthrax spores would likely continue to pose a threat of infection long after the initial release. Although the anthrax vaccine has been in commercial production for more than four decades and has been safely administered to more than a million adults in the military, it has never been tested with children. Thus the vaccine’s safety and effectiveness (immunogenicity) in children is unknown.

After the bioterrorism exercise, the National Biodefense Science Board recommended that the U.S. government conduct a study to test the safety and effectiveness of the vaccine in children, before an anthrax attack occurs, contingent upon a review of the ethical issues. Sebelius asked the commission to tackle the question.

The commission met four times to consider the ethical issues. The members had to weigh several ethical considerations, Arras explained.

The act of testing on children would expose them to a vaccine with unknown health risks, to prepare for a hypothetical attack with unknown probability of occurring. Such an attack might never happen.

Children in anthrax vaccine studies are very unlikely to benefit personally because, while experts debate the chance of a future anthrax outbreak anywhere on American soil, the chance of an outbreak in one particular location – where any given child test subject resides – is miniscule, Arras said.

(If an anthrax attack does occur, the ethical calculus is much different, as every child stands to personally benefit from post-event testing. Planning for post-event studies should begin now, the commission advised.)

A longstanding ethical principle holds that children are not able to give consent and cannot be used merely as a means to gain a public good, such as better preparedness for an anthrax outbreak, Arras said. In contrast, an adult can recognize the risks of anthrax vaccine testing and volunteer to participate.

Parents must give permission for their children to participate in research, but the children must also assent for themselves, if able, Arras said. Some proponents of testing told the commission that first responders are one community that might volunteer their children for this testing.

“This is a hard, hard issue,” Arras said. “Important points have been made on both sides.”

Ultimately, the commission advised that testing on children could be ethically acceptable only if researchers could take steps to demonstrate that the children would face no more than “minimal risk,” such as the normal side effects of a blood draw, or “a minor increase over minimal risk,” such as needing to stay home from school for a few days due to a reaction to a shot. In the latter case, researchers would have to seek the approval of a national-level panel that would have to follow a rigorous ethical framework designed and recommended by the commission.

The National Biodefense Science Board had concluded that any testing of the vaccine on children would present more risk than that allowed under either of the above tests, because its effects on children are unknown. However, the Bioethics Commission disagreed, noting that researchers may be able to stay within the “minimal risk” parameter by testing the vaccine first with 18-year-olds, determining its safety, then 17- and 16-year-olds, then 15- and 14-year-olds, and so forth, gradually ratcheting back the age of the test subjects to infancy, Arras said, “as long as, at each step, we can confidently predict there won’t be more than minimal risk.”

If such an inference is impossible and a national-level review is necessary, a research proposal must go through a process known as “Section 407 review,” recommended in the 1970s by a previous national bioethics commission, but with sketchy guidance on the exact criteria involved. The new 162-page report devotes more than 20 pages to better defining how to carry out a Section 407 review of research with children involving “minor increase over minimal risk” and “no prospect of direct benefit to healthy participants.”

“Fleshing out Section 407 may ultimately be one of the biggest results of this report,” Arras said.

The new report has been met with mixed responses, according to media coverage. Some quoted sources have claimed that the recommendations make testing virtually impossible, while others have said the studies will slowly but surely be done.

Arras said he does not know whether the studies will be done or not, but that question should not alter the ethical conclusion. At its heart, the commission’s guidance was based on the fundamental ethical conclusion that “you don’t subject children to serious harms or health risks when they do not stand to personally benefit, solely for the benefit of other people. That’s a bright line in ethics. That’s the big bullet we bit, knowingly and intentionally” – even though it means there is the possibility that testing will not happen before an anthrax outbreak occurs.

“This was a report that kept me and many of my colleagues up at night,” he said.